Pathogenesis/Genetics of frontotemporal lobar degeneration and how it relates to ALS

One of the most interesting findings in the field of neurodegeneration in recent years is tfche discovery of a genetic mutation in the C9orf72 gene, the most common mutation found to be causative of sporadic and familial frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and concomitant FTD-ALS (DeJesus-Hernandez et al., 2011b; Renton et al., 2011). While clinical and molecular data, such as the identification of TDP-43 being a common pathological protein (Neumann et al., 2006) have hinted at such a link for years, the identification of what was formally known as “the chromosome 9 FTLD-ALS gene” has provided a foundation for better understanding of the relationship between the two. Indeed, it is now recognized that ALS and FTLD-TDP represent a disease spectrum. In this review, we will discuss the current genetic and pathological features of the FTLD-ALS spectrum.